Transcript Ulcerative colitis

Inflammatory bowel diseases
(I.B.D)
IBD
TWO MAIN FORMS:
ULCERATIVE COLITIS- AFFECTS LARGE BOWEL
ONLY
CROHN’S DISEASE- AFFECTS ANY PART OF GIT
Epidemiology of IBD
Incidence (US)
Age of onset
Male:female ratio
Smoking
Oral contraceptive
Ulcerative colitis Crohn’s disease
11/100 000
7/100 000
15-30 & 60-80
15-30 & 60-80
1:1
1,1-1,8:1
May prevent
disease
May cause disease
No increased risk Relative risk 1,9
Appendectomy
Not protective
Protective
Monozygotic twins 8% concordance 67% concordance
High
Medium
Low
Epidemiology UC
► Highest
incidence in
Europe, United
Kingdom,
North America
Incidence per
person-years
2.2–14.3/100,000
Age of onset
15–30 & 60–80
Male:female ratio
1:1
Smoking
May prevent
disease
Oral contraceptives
No increased risk
Appendectomy
Protective
Monozygotic twins
6% concordance
Dizygotic twins
0% concordance
Epidemiology Crohn,s disease
Incidence: 7/100 000
pop/yr
World wide distribution
but more common in
the West.
The incidence is lower in
non-white races.
Females are
affected more
than males
1.2:1
Epidemiology
Jews are more affected
than non-Jews
Bimodal age distribution:
20-40 yrs/60-80 yrs
Prevalence: 100/100 000 pop/yr
The incidence is rising
Etiology
► Genetic
► Defective
immune regulation
► Exogenous factors
Etiology & Pathogenesis
The aetiology of IBD disease is unknown. There are many proposed
pathogenic mechanisms, some of which are represented in this diagram.
Genetic
susceptibility
Environmental
factors
Host
Immune
Response
IBD
As there is no one cause, it is likely that IBD disease is an outcome of
interactions between genetic predisposition, environmental factors and the
subsequent reaction of the host immune system.
Genetic:
► IBD
patients have disease-associated foci on
chromosome 16, 12,7,5,3,1 (gene NOD-2)
► Ulcerative colitis express HLA DR2 and CD
express DR5 DQ1, DRB0301.
► IBD patients with HLA DRB10130, have
extensive disease and extraintestinal
manifestation such as : mouth
ulcers,arthritis,uveitis
Immune dysregulation in IBD
NORMAL
normal
IBDIBD
Antigen and flora
Antigen and flora
Dysregulation ?
CD4+ T
Inhibitory cytokines
IL-10,TGF-b
CD-TH1
CD -TH2
IL-4,IL5,IL13
ING- ,TNF
Inflammatory cytokines
Oral tolerance
Crohn,s colitis
Ulcerative colitis
Pathology
Ulcerative colitis :
(1)Is a mucosal disease of colon
(2) 40-50% involve rectum ,30-40%
rectosigmoid ,20% pancolitis
(3) Backwash ileitis :10-2%%
(4) Mucosa is erythematous , hemorrhage
,ulcerations , pseudopolyps
Pathology( crohn,s):
► Affect
any part of GI from mouth to anus
► 30-40% small bowel
► 40-55% small and large bowel
► 15-25% alone colitis,” cobblestone”
► 90% terminal ileum is involved
► is a transmural disease with skip area , rectum is
spared ,preanal lesion like fistula ,fissures ,
abcesses,anal stenosis in see in 30%.
Normal colon
ULCERATIVE COLITIS
CONTINUOUS INVOLVEMENT
CROHNS vs PM COLITIS
Clinical:
► Intestinal
► Extraintestinal
Ulcerative colitis
Disease distribution
Ulcerative Colitis
Left sided
cloitis
Proctitis
Proctosigmoiditis
Disease distribution
► The
disease typically is most severe distally
and progressively less severe more
proximally.
►
In contrast to Crohn's disease, continuous
and symmetrical involvement is the hallmark
of UC, with sharp transition between
diseased and uninvolved segments of bowel
Clinical Features
diarrhea
tenesmus
rectal
bleeding
passage
of mucus
urgency
abdominal
pain
Clinical Features
The onset of UC typically is slow and insidious.
Symptoms have usually been present for weeks or months by the time the
patient seeks medical attention.
The median interval between the onset of symptoms and diagnosis of UC
is approximately 9 months.
Some patients with UC may present much more acutely, with symptoms
mimicking infectious colitis.
Intestinal symptoms of UC
► Diarrhea,
rectal bleeding ,tenesmus,
passage of mucus crampy pain, incomplete
evacuation.
► Intestinal complications : bleeding, toxic
colon, perforations , obstructions
Intestinal symptoms of CD :
► Ileocolitis
: diarrhea and chronic RLQ pain
► Jejunoileitis :malabsorption
► Colitis :diarrhea, low grade fever,pain, some
times hematochezia
► Gastroduodenal : G.O.O
► Intestinal complications :fistula, perforation,
intestinal obstruction, hemorrhage, preanal
diseases.
Extraintestinal
Manifestations of IBD
 Skin




Erythema nodosum
Pyoderma gangrenosum
Joints
Peripheral arthritis
Sacroileitis
Ankylosing spondylitis
Eye
Uveitis
Episcleritis
Iritis
Hepatobiliary complications
Gallstones
PSC
Renal complications
Nephrolithiasis
Recurrent UTIs
Extraintestinal complications of I.B.D
Oral :
Dermatologic :
(1)Erythema nodosum, CD, 15%
(2)Pyoderma gangrenosum , UC ,1-12%
Extraintestinal complications of I.B.D
Rheumatologic :
(1)Peripheral arthritis, CD,15-20%
(2)Ankylosing spondylitis : CD, 10%, and 2/3 have
positive test fir HLA-B27,no relation to activity
(3)Sacroiliitis :CD=UC, No relation to activity
Extraintestinal complications of I.B.D
Ocular :1-10%
(1)Conjuntivitis
(2)Anterior uveitis/iritis
(3)Episcleritis
Extraintestinal complications of I.B.D
Hepatobiliary:
(1)Hepatic steatosis :50%
(2)Cholelithiasis : CD>UC is seen in 10-35%
patients with ileitis
(3) Primary sclerosing cholangitis :1-5%of
I.B.D patients have PSC
50%-75 of patients with PSC have I.B.D
(4)Peicholangitis :
Extraintestinal complications of I.B.D
Urologic :
(1)Calculi :CD, 10-20%
(2)Ureteral obstruction
(3)fistula
Lab in IBD
► In
ESR,CRP, Hb
► PANCA :Is positive in 5% population, 5-10%
in first degree relatives 5-10% in CD , 6070% in UC
► ASCA : 5% Population ,10-15% in UC, 6070% in CD
► ANCA positivity is more associated with
pancolitis, early surgery, pouchitis, PSC.
Medical treatment
(1)Sulfasalazine
Adverse Effects of Sulfasazine
Dose related
► nausea
► vomiting
► anorexia
► folate malab.
► Headache
► alopecia
Not dose related
► skin rash
► hemolytic anemia
► agrannulocytosis
► fibrosing alveolitis
► hepatitis
► male infertility
► colitis
Newer therapy:
(2) 5-ASA
a-azo-band : olsalazine
b-5-ASA dimer(resin) :delayed
release, pH dependent , Asacol
c: sustained released:
ethylcellulose microgranules ,
PENTASA
Treatment (continuous):
(3)Glucocorticoids :
a-oral
b-Iv
c-suppository and enema
(4) Antibiotics : metronidazole, ciprofloxacin.
fistula , preanal lesions
(5)Azthioprine,,methotrexate,cyclosporine(iv dose2-4mg/kg
82% effective in UC refractory to therapy )
6-MP
(6)Anti-TNF antibody (infliximab) : dose 5mg/kg ,65% of
refractory CD respond,repeat every 8 weeks.
Treatment protocol
is based in two factors:
► Colonic
► DAI
involvement extent
Disease distribution
Ulcerative Colitis
Left sided
cloitis
Proctitis
Proctosigmoiditis
FACTORS MODIFYING RISK
Cancer risk in IBD:
OF COLITIS-ASSOCIATED
CANCER
Primary sclerosing
cholangitis
Family history of
colorectal cancer
pseudopolyp
Cancer in I.B.D
Sporadic colonic cancer (SCC) arise from adenomatous
polyp; colitis associated colonic cancer(CACs ) arise from
flat dysplasia or dysplasia-associated lesion or mass
(DALM)
► Multiple synchronous cancers occurs in3-5% SCC and in
12% CAC
► Mean age SCC is 60 and CAC 30 years
► SCC exhibits a left- sided predominance ,CAC distribute
uniformly
► Mucinous and anaplastic cancers are more common in CAC
than SCS
►
Inflammatory bowel diseases &
pregnancy
► Patients
with quiescent UC and CD have normal
fertility rates
► With increased activity patients have chance of
abortion , stillbirths and developmental defects,
but not due to medications
► Antibiotics like ampicillin,
cephalosporin,ormetronidazole for short
courses are safe
► Methotrexate and ciprofloxacin are contraindicated
► Sulfasalazine , 5-ASA and Glucocorticoids are safe
Indications for surgery:
Ulcerative colitis
Intractable disease
Fulminant disease
Toxic megacolon
Colonic perforation
Massive colonic
hemorrhage
Extracolonic disease
Colonic obstruction
Colonic cancer
Crohn,s disease
CD of small intestine:
Stricture,obstruction,fistula
Refractory to medical
therapy
Abscess
CD of colon and rectum:
Intractable
Preanal disease,fistula,
obstruction refractory to
therapy
cancer